Clusters of nuclear factor I binding sites identify enhancers of several papillomaviruses but alone are not sufficient for enhancer function.
Clusters of nuclear factor I binding sites identify enhancers of several papillomaviruses but alone are not sufficient for enhancer function.
复制标题
核因子 I 结合位点簇可识别多种乳头瘤病毒的增强子，但单独不足以发挥增强子功能。
作者：
B. Gloss;M. Yeo;M. Meisterenst;L. Rogge;E. Winnacker;H. Bernard
人乳头瘤病毒(HPV)的长控制区(LCR)包含病毒基因组的5-12%，并包含一个错综复杂的顺式反应元件网络。在HPV-1、HPV-6、HPV-8、HPV-11、HPV-16、HPV-18和HPV-33的LCR中，我们发现了4到7个5-TTGGC-3基序的簇，提示核因子I(NFI)结合位点。我们随机选择了这些基序中的20个(总共38个)，并表明从猪肝脏中提取的纯NFI保护的核苷酸与粗制HeLa核提取液中存在的一个因子几乎相同。在竞争实验中，用HeLa提取物在HPV-16的LCR中获得的足迹被代表回文腺病毒NFI结合位点的寡核苷酸消除。来自HPV-11、16和18基因组的限制性片段包含与无关转录因子的结合位点相关的这一簇NFI结合位点，其功能是转录增强子。相反，来自HPV-8的仅显示NFI结合位点的片段或来自HPV-16的聚合的NFI位点在功能上是不活跃的。NFI似乎是HPV增强子激活所必需的，但不是充分的。
The long control region (LCR) of human papillomaviruses (HPV) encompasses 5-12% of the viral genome and contains an intricate network of cis responsive elements. In the LCR of seven unrelated HPV-types, namely HPV-1, 6, 8, 11, 16, 18 and 33, we have identified clusters of 4 to 7 5-TTGGC-3 motifs suggesting nuclear factor I (NFI) binding sites. We randomly selected 20 (out of a total of 38) of these motifs and showed that pure NFI from porcine liver protects virtually the same nucleotides as a factor present in crude HeLa nuclear extracts. The footprints obtained with HeLa extracts in the LCR of HPV-16 are eliminated in competition experiments by an oligonucleotide representing the palindromic adenovirus NFI binding site. Restriction fragments from the genome of HPV-11, 16 and 18, which contain this cluster of NFI binding sites associated with binding sites of unrelated transcription factors, function as transcriptional enhancers. In contrast, a fragment from HPV-8 exhibiting exclusively NFI binding sites, or polymerized NFI sites from HPV-16, are functionally inactive. NFI seems to be necessary but not sufficient for HPV enhancer activation.